What is the role of steroids, such as prednisolone (corticosteroid), in the treatment of patients with moderate to severe alcoholic hepatitis?

Role of Steroids in Alcoholic Hepatitis

Prednisolone 40 mg daily for 28 days is the standard first-line treatment for severe alcoholic hepatitis (Maddrey Discriminant Function ≥32 or MELD >20), improving short-term survival by 41% in appropriately selected patients without contraindications. 1, 2

Patient Selection and Severity Assessment

Identify candidates for steroid therapy using validated prognostic scores to define severe disease:

• Maddrey Discriminant Function (MDF) ≥32 is the primary threshold for treatment consideration 1, 2
• MELD score >20 (or possibly >21) should also prompt steroid consideration 1, 3
• Patients with hepatic encephalopathy qualify regardless of other scores 2
• Mild alcoholic hepatitis (MDF <32, MELD <18) generally improves with abstinence and supportive care alone, without requiring steroids 2

Mandatory Pre-Treatment Screening

Before initiating steroids, you must exclude contraindications through systematic evaluation:

Absolute Contraindications 1, 2, 4:

• Active or uncontrolled infection (screen with blood cultures, urine cultures, chest x-ray, and ascites fluid culture if present)
• Acute kidney injury with serum creatinine >2.5 mg/dL
• Uncontrolled upper gastrointestinal bleeding
• Concomitant acute pancreatitis
• Multiorgan failure or shock
• Active infections: HBV, HCV, HIV, tuberculosis

The American Association for the Study of Liver Diseases emphasizes that infections are present in 12-26% of patients at admission, with up to half developing infection during steroid treatment, making pre-treatment screening critical 1, 4

Treatment Protocol

Standard Regimen 1, 2, 4:

• Prednisolone 40 mg orally daily (or methylprednisolone 32 mg IV equivalent) for 28 days
• Concurrent enteral nutrition with goal of >21 kcal/kg daily (or 30-40 kcal/kg/day with 1.2-1.5 g protein/kg/day) 1, 4
• Vitamin supplementation including thiamine, B12, folate, pyridoxine, vitamin D, and zinc 4

Optional Adjunctive Therapy:

• N-acetylcysteine with corticosteroids may improve 1- and 3-month survival, though not consistently recommended pending confirmatory studies 2

Critical Early Response Assessment

The Lille score at day 7 determines whether to continue or stop steroids - this is the most important decision point in management:

Lille Score Interpretation 2, 5, 4, 6:

• Lille <0.45 (responders): Continue prednisolone for full 28 days - these patients have 85-91% 28-day survival
• Lille 0.45-0.56 (partial responders): Consider stopping on case-by-case basis - 79.4% 28-day survival
• Lille ≥0.56 (null responders): Stop steroids immediately - only 53.3% 28-day survival, no benefit from continued therapy, only increased infection risk

The American Association for the Study of Liver Diseases emphasizes that continuing steroids in non-responders (Lille ≥0.56) is a critical error that exposes patients to infection without survival benefit 4

Alternative Early Assessment:

• Day-4 Lille score is as accurate as day-7 assessment and can identify non-responders earlier to limit futile steroid exposure 6

Therapeutic Window and Efficacy

Steroids are only effective within a specific disease severity range:

• Maximum benefit occurs with MELD scores between 25-39, showing 21-30% survival improvement 3
• Minimal benefit threshold: MELD 21 (hazard ratio 0.61) 3
• Upper limit of benefit: MELD 51 - no survival benefit above this threshold 3
• Overall mortality reduction: 41% decrease in 30-day mortality (hazard ratio 0.59) in appropriate candidates 3

The landmark 1992 trial demonstrated 88% survival with prednisolone versus 45% with placebo at 66 days in severe alcoholic hepatitis 7

Alternative Therapy When Steroids Contraindicated

Pentoxifylline 400 mg three times daily for 28 days can be considered when steroids are contraindicated, though it is clearly inferior 1, 2, 4:

• Korean trial showed 74.5% 1-month survival with pentoxifylline versus 87.0% with prednisolone 1
• Combination therapy of steroids plus pentoxifylline provides no additional benefit over steroids alone 1, 8
• Do not use pentoxifylline as rescue therapy in steroid non-responders - it provides no benefit 1, 4

Management of Non-Responders

If patient worsens despite prednisolone or has Lille ≥0.56:

1. Stop steroids immediately 4
2. Screen extensively for infection - blood cultures, urine cultures, chest x-ray, ascites fluid culture 4
3. Consider early liver transplantation evaluation in carefully selected patients 1, 4
4. Recognize that 25% of patients develop infection during the first month of steroid treatment, with clinical deterioration indicating very high infection risk 4

Long-Term Outcomes and Critical Caveats

Steroid benefit is primarily short-term:

• Survival advantage persists at 1 year (69-71% in treated vs 41-50% in untreated) but diminishes by 2 years 9
• Long-term survival depends primarily on achieving alcohol abstinence, which must be strongly promoted to all patients 2, 4
• Patients with marked liver polymorphonuclear infiltrate have better response to steroids (76% 1-year survival versus 53% without infiltrate) 9

Common Pitfalls to Avoid

• Never continue steroids beyond day 7 in non-responders - this only increases infection risk without survival benefit 5, 4
• Do not use anti-TNF-α agents (infliximab, etanercept) - these increase mortality due to serious infections 1
• Avoid nephrotoxic drugs including IV contrast, aminoglycosides, NSAIDs, and use diuretics cautiously 1
• Do not treat patients with MELD >51 - steroids provide no benefit in this extremely severe population 3